CN1456334A - Preparation of Qingkailing injection - Google Patents

Abstract

A process for treating Chinese medicine "Qingkailing injection" features that its filter step is improved to three-stage filter. For the first stage, the positive-pressure filter-bag capture with 5-10 microns of aperture is used. For the second stage, the positive-pressure folded cylindrical or plate (0.05-0.2)-micron membrane filter made of postively charged material is used. For the third stage, the positive-pressure folded cylindrical or plate (0.2-0.45)-micron membrane filter made of positively charged material is used. It can increase the qualified rate of products to 99-100%.

Description

The QINGKAILING ZHUSHEJI new preparation process

Affiliated technical field

The present invention relates to a kind of is the improvement of the injection preparation method of primary raw material with the Chinese crude drug, specifically relates to filter among the QINGKAILING ZHUSHEJI preparation technology method improvement of operation.

Background technology

QINGKAILING ZHUSHEJI be a kind of be the injection of primary raw material with the Chinese crude drug, this product has heat-clearing and toxic substances removing, the effect of tranquillizing and allaying excitement, cure mainly urgency, chronic hepatitis, heavy cold, diseases such as hyperpyrexia, this product was gone on the market in China in nineteen eighty-two, nineteen ninety-five is classified as essential drugs by ministry of Health of China, the preparation method of QINGKAILING ZHUSHEJI was except its medicine material adopted specific extraction and preparation technique at that time, its preparation process has adopted the common process of injection basically, it is dosing, filter, embedding, sterilization, and filterable method is to adopt filter paper, filtrations such as pottery core or sand rod are after the microporous membrane filtration of 0.2～0.45 μ m.The medicine liquid irrigation of handling through the such filtration operation sterilization of being honored as a queen, by the state-promulgated pharmacopoeia standard detection, often occur after underproof phenomenon of thermal source and the medication anaphylaxis being arranged, the qualification rate that causes product because of thermal source is defective is only 70～90%, so the production cost height of factory.For this reason, must the underproof phenomenon of thermal source occur, improve the qualification rate and the drug safety of product from the production technology solution of QINGKAILING ZHUSHEJI.

Summary of the invention

The objective of the invention is to improve the production technology of QINGKAILING ZHUSHEJI, the underproof phenomenon of thermal source appears in solution, improves the quality and the qualification rate of product.

For implementing the technical scheme that purpose of the present invention adopts be: the preparation technology of QINGKAILING ZHUSHEJI, be to comprise by the raw material cholic acid, hyodeoxycholic acid, Cornu Bubali, Concha Margaritifera, baicalin, Fructus Gardeniae, Radix Isatidis, Flos Lonicerae is carried or the hydrolysis extraction through water, the medicinal liquid (1) that the QINGKAILING medicinal liquid of making is regulated behind the pH value with sodium hydroxide solution gets clear and bright QINGKAILING medicinal liquid (4) through filtering operation, embedding gets QINKAILING ZHUSHEYE in ampoule or infusion bottle, laggardly go into sterilization, lamp inspection, packing, the present invention has done improvement in the filtration operation, adopt three-stage filtration technology, the first order is the pressure of medicinal liquid (1) at 0.05～0.15Mpa, under 10～80 ℃, filtering velocity is via hole diameter 5～10 μ m filter bag type catcher (5) coarse filtration under 0.4～1.5 ten thousand ml/min, malleation circulating filtration 1～2 time; The second level is the pressure of medicinal liquid (2) at 0.05～0.15Mpa, 10～80 ℃ of temperature, filtering velocity is under 0.4～1.5 ten thousand ml/min, the membrane filter (6) of foldable type tubular through making with strong positive charge material or tabular aperture 0.05～0.2 μ m, malleation circulating filtration 1～3 time; The third level is that medicinal liquid (3) is at pressure 0.05～0.15Mpa, 10～80 ℃ of temperature, filtering velocity is under 0.4～1.5 ten thousand ml/min, foldable type tubular of making through positively charged material or the efficient membrane filter (7) of tabular aperture 0.2～0.45 μ m filter 1～2 time medicinal liquid (4).

Because this filtration operation is to have adopted positive press filtration, as hypotony, filtering velocity slows down, production efficiency is low, and the pressure height, filtering velocity is fast, but filter membrane is perishable, and can not guarantee the quality of product, the temperature of medicinal liquid also has certain influence to the rate of filtration during filtration, filtering velocity is relevant with the character of pressure, medicinal liquid, temperature and used circulating pump, is under 0.4～1.5 ten thousand ml/min to adopt the first order to filter to be pressure at 0.1～0.15Mpa, 20～80 ℃, filtering velocity, via hole diameter 5 μ m filter bag type catcher circulating filtrations 1～2 time; Filter the second level is pressure at 0.1～0.15Mpa, and 20～70 ℃, filtering velocity is under 0.4～1.5 ten thousand ml/min, filters 1～2 time through the membrane filter (6) of foldable type tubular aperture 0.05～0.2 μ m; The third level is at pressure 0.05～0.15Mpa, and 20～60 ℃ of temperature, filtering velocity are that the efficient membrane filter (7) through foldable type tubular aperture 0.2 μ m is filtered into good under 0.4～1.5 ten thousand ml/min.

The preparation technology of QINGKAILING ZHUSHEJI of the present invention has following advantage: 1; adopted three-stage filtration owing to filter operation; the first order is to adopt the pouched trapper of 5 bigger μ m of aperture to make coarse filtration; the big slightly microgranule of elimination; protect second level filter membrane to be difficult for stopping up simultaneously; the second level is 0.05～0.2 μ m aperture; filter membrane is that a kind of special material with strong positive charge is made; and the normally electronegative fine particles of pyrogen and allergin; it can be by the general filter material of aperture 0.2 μ m; but under the effect of positive electric field; these fine particles will be adsorbed and dam; and because operating procedure has adopted circulating filtration; guaranteed the filtering of the fine particles of these 0.05～0.2 μ m; guaranteed medicinal liquid apyrogeneity and allergin, the filter membrane of the third level 0.2 μ m also is to have adopted positively charged special material to make the micropore filter material to make the high filter effect of tool; thoroughly all antibacterials of filtering and be the negative charge microgranule have further guaranteed the aseptic and clear and bright of medicinal liquid.2, because the filtration operation is pressure filtration, and overall process remains on malleation, and outside air is difficult for penetrating the filtration system, and filterable quality is more stable, be fit to the big technology of volume of production.3, can not pollute medicinal liquid, not influence the pH value and the medicament contg of medicinal liquid, guarantee the quality of injection, the defective occurrence rate of the pyrogen reaction of product is almost nil, and the qualification rate of product can reach 99～100%.

The preparation technology of the said QINGKAILING ZHUSHEJI of the present invention is described in detail in detail below in conjunction with drawings and Examples.

Description of drawings Fig. 1, be preparation technology's flow chart of the said QINGKAILING ZHUSHEJI of the present invention.Number in the figure: 1. 2. 3. 4. 5. catcher 6. membrane filters 7. efficient membrane filter 8. centrifugal pumps 9. Pressure gauges 10. valves of medicinal liquid (4) of medicinal liquid (3) of medicinal liquid (2) of medicinal liquid (1), the control medicinal liquid flows to 11. air bleeding valves, 12. embedding operations, 13. sterilization process, 14. drain valves

Embodiment 1

See shown in Figure 1, take by weighing raw material by recipe quantity, it is 20L that existing technology is in accordance with regulations extracted behind the preparation QINGKAILING medicinal liquid with medicinal liquid (1) volume behind 10% the sodium hydroxide solution adjusting pH value to 7.8, fluid temperature is 75 ℃, with centrifugal pump 8 medicinal liquid (1) is squeezed into catcher 5, be controlled at 0.1Mpa, circulating filtration is 2 times under filtering velocity 1.2 ten thousand ml/min, get medicinal liquid (2), remain on 70 ℃, 0.1Mpa pressure, under filtering velocity 1.0 ten thousand ml/min through membrane filter 6, filter membrane in the filter is that to adopt commercially available model be the filter element that the foldable type tubular filter membrane of ZETAPLUS-90LP or 90SP is made, circulating filtration 2 times, the medicinal liquid sampling that leaches, lamp inspection, clarity is qualified, remain on 65 ℃, 0.1Mpa pressure, filtering velocity 1.0 ten thousand ml/min directly enter efficient membrane filter 7, and the filter membrane in the filter is that the commercially available model of employing is the foldable type tubular element of ZETAPOR SP0.2 μ m, filters 1 time and gets filtrate (4), filtrate (4) enters embedding operation 11, the ampoule that embedding becomes 10ml/ to prop up, the laggard operation 12 of going into to sterilize is finished in embedding.Finished product is pressed Chinese Pharmacopoeia standard detection pyrogen reaction, rabbit method, rabbit per kilogram of body weight injection 5ml QINKAILING ZHUSHEYE, apyrogeneity reaction; Press the Chinese Pharmacopoeia standard through the row abnormal toxicity test, dosage is by every injected in mice this product 0.5ml, no abnormal toxicity; Other every indexs all meet quality standard.

Embodiment 2

Operation with embodiment 1, one, two, the filter element that tertiary filter is used, filter membrane material is with embodiment 1, the temperature of medicinal liquid is 40 ℃, pressure 0.8Mpa when one-level is filtered, lamp inspection was defective after filtering velocity 0.8 ten thousand ml/min filtered 1 time, reflux and filter is 1 time again, and lamp inspection is qualified, enters cascade filtration, keeping temperature is 37 ℃, pressure 0.8Mpa enters three-stage filtration behind filtering velocity 0.8 ten thousand ml/min, circulating filtration 2 times, keeping temperature is 32 ℃, pressure 0.8Mpa, filtering velocity 0.8 ten thousand ml/min, the medicinal liquid behind three-stage filtration carries out embedding, sterilization, detect every indexs such as pyrogen and no abnormal toxicity and all meet quality standard.

Claims (2)

1, a kind of preparation technology of QINGKAILING ZHUSHEJI, it comprises by the raw material cholic acid, hyodeoxycholic acid, Cornu Bubali, Concha Margaritifera, baicalin, Fructus Gardeniae, Radix Isatidis, the QINGKAILING medicinal liquid that Flos Lonicerae is made is regulated medicinal liquid (1) behind the pH value through filtering the clear and bright QINGKAILING medicinal liquid (4) of operation with sodium hydroxide solution, embedding gets QINKAILING ZHUSHEYE in ampoule or infusion bottle, laggardly go into sterilization, lamp inspection, packing, it is characterized in that: filter operation and adopt three-stage filtration, first order medicinal liquid (1) is at pressure 0.05～0.15Mpa, 10～80 ℃ of temperature, filtering velocity is under 0.4～1.5 ten thousand ml/min, via hole diameter 5～10 μ m filter bag type catcher (5) coarse filtration, malleation circulating filtration 1～2 time; The second level is the pressure of medicinal liquid (2) at 0.05～0.15Mpa, 10～80 ℃ of temperature, filtering velocity is under 0.4～1.5 ten thousand ml/min, the membrane filter (6) of foldable type tubular through making with strong positive charge material or tabular aperture 0.05～0.2 μ m, malleation circulating filtration 1～3 time; The third level is that medicinal liquid (3) is at pressure 0.05～0.15Mpa, 10～80 ℃ of temperature, filtering velocity is under 0.4～1.5 ten thousand ml/min, foldable type tubular of making through positively charged material or the efficient membrane filter (7) of tabular aperture 0.2～0.45 μ m filter 1～2 time medicinal liquid (4).

2, the preparation technology of QINGKAILING ZHUSHEJI according to claim 1, it is characterized in that, it is that pressure, 20～80 ℃, filtering velocity at 0.1～0.15Mpa is under 0.4～1.5 ten thousand ml/min that the first order is filtered, through aperture 5 μ m filter bag type catcher circulating filtrations 1～2 time; Filter the second level is pressure at 0.1～0.15Mpa, and 20～70 ℃ of filtering velocitys are under 0.4～1.5 ten thousand ml/min, filters 1～2 time through the membrane filter (6) of foldable type tubular aperture 0.05～0.2 μ m; The third level is at pressure 0.05～0.15Mpa, and 20～60 ℃ of temperature, filtering velocity are that the efficient membrane filter (7) through foldable type tubular aperture 0.2 μ m filters under 0.4～1.5 ten thousand ml/min.